In the suprachiasmatic nucleus, the brain’s central pacemaker, CLOCK (circadian locomotor output cycles kaput) is a transcription factor that plays a crucial role in regulating circadian rhythms. However, this protein also appears outside this region, in the cerebral cortex, where its function is still unclear. A new study, published today (October 11) in Neuron, suggests that the loss of CLOCK in the cortex is associated with certain severe forms of epilepsy.

Prior studies have provided hints of a link between epilepsy and our sleep-wake cycles. For example, researchers have observed that seizures tend to follow circadian rhythms, and that some individuals are more susceptible to seizures during sleep. Others have reported, based on animal experiments, that changes in the expression of clock genes, such as Bmal and Per, may be associated with the disease.

Although they ultimately arrived at a circadian gene, Judy Liu, a neurologist and professor at Brown University, and her colleagues had not set out to study it. Instead, she says, “we were trying to figure out what’s different from epilepsy tissue compared with normal brain.”

“[This study provides] an intriguing take on the role of CLOCK and epilepsy,” says Omar Ahmed, a neuroscientist at the University of Michigan who did not take part in the work. “What’s interesting [is] that this gene is known to be expressed in the neocortex, but it’s not known what it does there. . . . CLOCK mostly carries out its circadian function in the [suprachiasmatic nucleus].” Because the control tissue also came from patients, one important question to address, he adds, is whether Clock expression is reduced in brain areas where seizures occur or if it has, instead, gone up in nearby healthy tissue.